• EFFECTS OF SODIUM BICARBONATE ON GLUCOSE HOMEOSTASIS AND BLOOD PRESSURE IN CHRONIC KIDNEY DISEASE

      Mannon, Elinor; Department of Philosophy (Augusta University, 2021-10)
      Sodium bicarbonate (NaHCO3) is a therapeutic used in chronic kidney disease (CKD). NaHCO3 is typically used to treat metabolic acidosis, but clinical studies have indicated that NaHCO3 supplementation may slow CKD progression. As such, NaHCO3 is now given to patients with CKD to slow the decline of glomerular filtration rate. However, the consequences of chronic NaHCO3 supplementation in CKD remain unclear. Acidosis has been associated with insulin resistance, and correction of acidosis with NaHCO3 was reported to improve insulin sensitivity. Our goal in Aim 1 was to determine whether acid and alkali loading would promote loss of acid-base homeostasis and consequently decrease insulin sensitivity. We determined that the blood glucose response to insulin is enhanced following renal mass reduction, and that this response is not reversed by an acidosis. Additionally, the development of an alkalosis did not impair the blood glucose response to insulin. Alkali can promote potassium (K+) wasting, and an association between K+ wasting and insulin resistance has been identified in clinical and basic science research. Our goal in Aim 2 was to identify whether chronic NaHCO3 treatment may promote loss of insulin sensitivity through effects on K+ status. We determined that chronic NaHCO3 treatment impairs insulin sensitivity when combined with other K+ wasting stimuli. K+ deprivation alone also impaired the blood glucose response to insulin, however these impairments in insulin sensitivity were not directly related to decreases in intracellular [K+]. Salt-sensitivity increases as functional renal mass declines, and chronic sodium (Na+) loading with NaHCO3 may contribute to hypertension in patients with CKD. Our goal in Aim 3 was to investigate whether NaHCO3 loading promotes similar levels of Na+ and volume retention, and hypertension as sodium chloride (NaCl) loading does in a rat model of CKD. We found that NaHCO3 was pro-hypertensive, but to a lesser degree than NaCl, despite similar amounts of Na+ and volume retention. From these studies we concluded that NaHCO3 does not improve insulin sensitivity through its effects on acid-base status. Further, access to dietary K+ may improve insulin sensitivity with chronic NaHCO3 treatment. Finally, NaHCO3 can promote hypertension in CKD.
    • Bioactivity and mechanism of action of resveratrol, a polyhenolic phytoalexin, in sickle cell disease

      Agyekum, Davies G.; Medical College of Georgia (Augusta University, 2013-07)
    • Physicians' perceived incentives for association with nurse practitioners in the delivery of primary care

      Adinaro, Denise; School of Nursing (Augusta University, 1980-08)
      The purpose of this study was to identify those factors which physicians , currently associated with nurse practitioners, perceive as incentives in their motivation to associate with these nurse practitioners in providing primary care. A mail survey was sent to nurse practitioners and their associate physicians throughout the State of Georgia, with two follow-up postcard mailings. Data were collected for a 4 week period and a 30.46 return was obtained. A mean ranking of the identified incentives was performed. Two major categories of incentives were identified . To increase the quality of care was considered to be most important and to expand the services offered in general was rated second as incentives for physician association with nurse practitioners.
    • A NOVEL NETWORK BASED LINEAR MODEL FOR ENRICHMENT OF SYNERGISTIC DRUG COMBINATIONS

      Li, Jiaqi; Department of Physiology (Augusta University, 2021-07)
      Drug combination therapies can improve drug efficacy, reduce drug dosage, and overcome drug resistance with respect to cancer treatments. Current research strategies to determine which drug combinations have a synergistic effect rely mainly on clinical or empirical experience and screening predefined pools of drugs. Given the number of possible drug combinations, the speed and scope to find new drug combinations are very limited using these methods. Due to the exponential growth in these combinatorials, it is difficult to test all possible outcomes in the lab. Several large-scale public genomic and phenotypic resources that provide data from single drug-treated cells as well as data from small molecules deliver a wealth of cellular response information. This data gives opportunity to overcome limitations of the current methods. The development of a new strategy for advanced data processing and analysis that includes a computational prediction algorithm is highly desirable. Because of this, a program was written that predicts synergistic drug combinations using gene regulatory network knowledge and an operational module unit (OMU) system generated from single drug genomic and phenotypic data. As a proof of principle, we applied the pipeline to a group of anticancer drugs and demonstrated how the algorithm could help researchers efficiently find possible synergistic drug combinations using single drug data to evaluate all possible drug pairs.
    • Associations Between Social Determinants of Health and Net Stress

      Lassiter, Debbie Jo; Department of Physiological & Technological Nursing (Augusta University, 2021-12)
      Stress is known to cause dire physical and mental health outcomes. Extant stress research has lacked a subjective rapid screening tool for further evaluation of high risk individuals. Net stress is a new construct developed in this study as the calculation of an individual’s perceived average stress level compared with their perceived healthy stress level. Measuring net stress provides an additional construct to identify health disparities among individuals at potential risk for mental and physical illness. The two aims were first to develop the net stress construct and secondly to examine and evaluate the relationships between net stress and Social Determinants of Health (SDoH) domain variables from the 2018 Stress in AmericaTM survey developed by APA and The Harris Poll survey and analytics group. The five SDoH domains developed by Healthy People 2020 were Neighborhood and Built Environment, Health and Health Care, Social and Community Context, Education, and Economic Stability. The methods included an exploratory, secondary analysis which included multiple regression to test whether net stress would respond predictably as a valid, new construct within the sample from the survey (N = 3,091). Net stress was regressed on the groups of variables for each domain, then on a model with all variables to determine if there were substantial differences in how net stress responded. Conclusions for this study were that four of the five domains, excepting Education, had substantial associations (0.25 standard deviation) with net stress. Using slightly less restrictive criteria, net stress was associated with variables from all five SDoH domains. Results were that net stress responded as a valid, new construct within this analysis. This study found that individuals with the following circumstances had substantially higher net stress levels: larger household size up to eight residents, single parent family structure, having no insurance, having a low perceived health level, being of bisexual orientation, being female, and having low household income. The Economic Stability domain impacted all other domains. Implications for future research, healthcare practice, nursing theory, and policy were discussed.
    • Belief in Research, Religious Coping, and Willingness to Participate in Clinical Trials among African Americans with Hematologic Malignancies

      Petty, Marjorie Elizabeth; Department of Physiological & Technological Nursing (Augusta University, 2021-12)
      African Americans (AAs) are disproportionately affected by certain types of hematologic malignancies. Despite the efforts of investigators, AAs with hematologic malignancies remain grossly underrepresented in cancer clinical trials. Few studies have evaluated the underrepresentation of this subgroup of patients in the context of their willingness to participate in clinical trials. Yet, willingness to participate in cancer clinical trials among AAs with solid tumors is well documented. The aims of the present study were to determine if a relationship exists between belief in research and willingness to participate in clinical trials and determine if religious coping moderates the relationship between belief in research and willingness to participate in clinical trials. To address the aims, data on religious coping were captured at one time-point using the validated Brief RCOPE scale and also using researcher-generated questions that addressed beliefs associated with research and willingness to participate in cancer clinical trials. The results reported here show there was no statistical difference between belief in research and willingness to participate in clinical trials, and religious coping did not moderate the effect of belief in research on willingness to participate in clinical trials. Statistically significant differences were found between education and belief in research. Participants with less than a high school education had lower belief in research scores than those with some college education, who showed higher belief in research scores. These findings provide preliminary results that suggest future studies are warranted in the study of AAs' beliefs in research. Such studies may contribute to the development of educational interventions to improve the recruitment of AAs with hematologic malignancies into the therapeutic clinical trials for these diseases, with a particular emphasis on educational interventions for those AAs with less than high school education. The study highlights the need for researchers to develop tailored educational approaches on cancer clinical trials for AAs with less than high school education. Such considerations may improve patients’ decision-making and access to novel therapies that could benefit the individual and others. Furthermore, researchers need to assess religious coping methods and develop tailored religious coping strategies that can be implemented into the clinical setting for AAs with hematologic malignancies. Tailored religious coping strategies could improve patient wellness and minimize the consequences of maladaptive religious coping (Pargament et al., 2011) among AAs with hematologic malignancies. Keywords: African American, hematologic malignancies, cancer clinical trial
    • MODELING THE SIMULTANEOUS EFFECTS OF COPY NUMBER VARIATION AND METHYLATION ON GENE EXPRESSION USING NEXT GENERATION SEQUENCING DATA

      Claussen, Henry; Department of Physiology (Augusta University, 2021-07)
      The collection and order of nucleobases in a strand of DNA, called the primary sequence, is one of the most important pieces of information in the study of the human body. The proteins which regulate all biological functions in the body are synthesized based on the structure of the DNA molecule. The next generation sequencing (NGS) process of sequencing RNA transcripts, known as RNA-seq, has become a powerful alternative to traditional microarray technology. NGS is used to measure the levels of gene expression, detect structural DNA variations from the human reference genome, and uncover the epigenetic modifications of methylation. Despite its prevalence in genetic research, RNA-seq data suffers from the statistical complication known as ”large p small n” where the predictor variables greatly outnumber the subjects in a study. In this research we propose combining all three types of data into a multivariate linear model. With the implementation of a variable selection process for preliminary dimension reduction and the application of a Group LASSOapproach, we hope to reduce the complexity and dimension of NGS data to a manageable and, most importantly, interpretable level. Changes in gene expression levels have been linked with the development of harmful diseases such as cancer. A successful model will provide insight on the simultaneous effects that methylation and structural variation have on gene expression in the body.
    • Predictive Inference for Linear and Circular Concomitants with Biomedical Applications

      Howie, Melissa; Department of Philosophy (Augusta University, 2021-07)
      Let (X_i, Y_i), for i=1,...,n, be a random sample from a bivariate distribution. If the sample is ordered with respect to one of the variables, say X, then the rth ordered X-value is called the rth order statistic and is denoted X_{r:n}. The Y-value corresponding to this value is called the concomitant of the rth order statistic and is denoted Y_{[r:n]}. In biomedical research, there is an interest in predicting the concomitant variable corresponding to the rth order statistic of the other variable. For example, one may be interested in predicting the time at which a patient has the peak blood pressure or the mercury level in fish where the water is most polluted. One such distribution of interest is the bivariate exponential conditionals distribution (BEC), whose conditional distributions are both exponential. The asymptotic predictive distribution of the concomitants of order statistics from the BEC is derived. The results are used in a prediction problem involving the mercury concentration in largemouth bass sampled from Florida lakes, as a function of surface water pollution level. Clinicians are often confronted with data such that one variable is linear and the other variable is circular, i.e., measured as an angle. A particular linear-circular distribution of interest is the exponential circular normal distribution. The predictive distribution of concomitants of order statistics from the exponential circular normal distribution is derived. The results are applied to predicting the future value of time at maximum heart rate in subjects from the Augusta Heart Study, a longitudinal study of normotensive children with verified family histories of cardiovascular diseases (e.g., hypertension and premature myocardial infarction).
    • Studies on calcium transport of the sarcoplasmic reticulum in skinned cardiac muscle

      Zhu, Yu; Department of Physiology and Endocrinology (Augusta University, 1990-11)
    • Angiogenesis-associated gene expression changes in surgical skin flaps of diabetic rats

      Zhou, Miao Xian (Cindy); Medical College of Georgia (Augusta University, 2010-07)
    • Aquaporin 3 in keratinocyte differentiation

      Zhan, Xiangjian; Medical College of Georgia (Augusta University, 2003-08)
      Aquaporin 3 (AQP3) is a channel that transports both water and glycerol. AQP3- null mutant mice exhibit skin defects, including impairment of water holding capacity, barrier recovery and wound healing and decreased glycerol content. We hypothesized that AQP3 is involved in the regulation ofkeratinocyte proliferation and differentiation and this regulation is mediated, at least in part, by the functional interaction between AQP3 and phospholipase D (PLD). Here we demonstrate that AQP3 expression was down-regulated at the transcriptional level and glycerol uptake was reduced when primary mouse keratinocytes were induced to differentiate. In co-transfection experiments, we found that AQP3 decreased the promoter activity of keratin 5, a keratinocyte proliferation marker, but increased the promoter activity of keratin 10 and involucrin, an early and intermediate keratinocyte differentiation marker respectively. These results suggest that AQP3 is a regulator of early keratinocyte differentiation. In further investigatjons to determine the sigualing function of AQP3 in regulating keratinocyte differentiation, we found using sucrose gradient centrifugation, irnmunoprecipitation analysis, confocal microscopy that AQP3 and PLD2 were colocalized in lipid rafts. In addition, we demonstrated that AQP3 could contribute to the synthesis of phosphatidylglycerol (PG) and that PLD2 was able to utilize glycerol as a substrate to synthesize PG. These data suggest that AQP3 transports glycerol for use as a physiological primary alcohol substrate for-adjacent PLD2 to generate PG. Our results, together with the reports that PG is an activator of protein kinases (PKqm and PKCe) and also contributes to protein-protein interactions in membranes, suggest that glycerol AQP3-PLD2-PG is a potential signaling pathway in regulating keratinocyte differentiation.
    • EFFECTS OF ATTENUATION OF a8 AND a6 INTEGRINS ON THE DEVELOPMENT OF CIDCKEN OPTIC TECTUM

      Zhang, Zhiqiang; Medical College of Georgia (Augusta University, 1997-05)
    • Characterization of leydig cell development in the rat testis

      Zhai, Juan; Medical College of Georgia (Augusta University, 1996-05)
    • Social Determinants of Health Associated with Parental Hesitancy and Teen Human Papillomavirus Immunization

      Lee, Seth; Department of Physiological & Technological Nursing (Augusta University, 2021-08)
      Background: Human Papillomavirus (HPV) is the most prevalent sexually transmitted infection in the United States. HPV-preventive vaccination of teens may be blocked by parental hesitancy, related to negative social determinants of health in the community. Parental hesitancy is one of the most significant barriers to increasing teen HPV vaccine uptake. Aims: The first aim was to determine associations among social determinants of health domain variables and parent-reported vaccine hesitancy of HPV immunization. The second aim was to determine the model that best explains how social determinants of health affect parental vaccine hesitancy of HPV immunization for each of the five reasons not to vaccinate. Methods: This quantitative retrospective study used logistic regression to examine relationships among parent-reported reasons not to vaccinate teens and selected social determinants of health variables utilizing the Centers for Disease Control and Prevention National Immunization Survey-Teen 2018. Variable selection was guided by the Social Determinants of Health Framework, categorized into five key domains: economic stability, education, social and community context, health and healthcare, and neighborhood and built environment (N = 7480). Results: Bivariate associations emerged across reasons not to vaccinate; the most frequent associations included variables such as the education level of a teen's mother and language of the survey interview. Models from multivariable regression with backward elimination indicated that key issues within the domains of education, health and healthcare, and social and community context were associated with parental hesitancy of HPV immunization. Conclusion: Stakeholders should focus on key issues within the domains of education, health and healthcare, and social and community context when designing policy and providing HPV immunization to teens. Taken holistically, key issues within the domains of education, health and healthcare, and social and community context are more likely to lead to vaccine hesitancy based on the findings in this study and require an approach tailored to the needs of the community and its residents. More research is needed to verify these results.
    • The effect of dentin desensitizers on the retention of full crowns cemented with a variety of luting/bonding agents

      Yim, Nantiya Harnkul; Department of Oral Biology (Augusta University, 1999-04-21)
    • Structural and functional aspects of organic cation transporters

      Wu, Xiang; Medical College of Georgia (Augusta University, 1999-07)
    • Confidence interval estimation for a binomial proportion when no successes are observed

      Wimmer, Courtney; Dias, James; Medical College of Georgia (Augusta University, 2009-04)
      Confidence interval estimation for a binomial proportion is a long debated topic, resulting in a wide range of exact and approximate methods. Many of these methods perform quite poorly when the number of observed successes in a sample of size n is zero. In this case, the main objective of the investigator is usually to obtain an upper bound, i.e., the upper limit of a onesided confidence interval. Traditional notions of expected interval length and coverage probability are not applicable in this situation. In this paper we use observed interval length and p-confidence to evaluate nine confidence interval methods for a binomial proportion. We also consider approximate sample sizes needed to achieve various upper bounds near the zero boundary. We show that many popular approximation methods perform poorly based on these criteria and conclude that the-exact method has superior performance in terms of interval length and p-confidence.
    • A Variable prenatal stress paradigm as a valid drug discovery platform for cognitive deficits associatied with neuropsychiatric disorders

      Wilson, Christina Ann; Medical College of Georgia (Augusta University, 2012-10)
      Cognitive dysfunction is now recognized to be central to the functional disability of several neuropsychiatric disorders. However, treatment options for the management of cognitive symptoms are limited and the development of novel therapeutics has been made difficult by the lack of appropriate animal models. It has been suggested that variable prenatal stress (PNS) in rodents might be an etiologically appropriate model for some components of schizophrenia. Thus, the overall goal of this dissertation project was to conduct a comprehensive behavioral study of the model to assess face validity, and to make a preliminary assessment of its construct and predictive validity. Our results indicate that exposure to PNS results in elevated corticosterone levels following exposure to acute stress, increased aggressive behaviors, as well as increased locomotor activity and stereotypic behaviors. Further, PNS rats had altered innate fear responses to predator odor as well as impaired fear extinction. Additionally, PNS in rats was associated with impairments of sustained attention, inhibitory response control, and recognition memory all of which could be attenuated by the norepinephrine reuptake inhibitor, atomoxetine. Collectivity, these data ,support the premise that PNS in rodents is a valid model system for studying some behavioral components of neuropsychiatric disorders as well as their treatment.